Common deletion polymorphisms in the human genome (original) (raw)

Nature Genetics volume 38, pages 86–92 (2006)Cite this article

Abstract

The locations and properties of common deletion variants in the human genome are largely unknown. We describe a systematic method for using dense SNP genotype data to discover deletions and its application to data from the International HapMap Consortium to characterize and catalogue segregating deletion variants across the human genome. We identified 541 deletion variants (94% novel) ranging from 1 kb to 745 kb in size; 278 of these variants were observed in multiple, unrelated individuals, 120 in the homozygous state. The coding exons of ten expressed genes were found to be commonly deleted, including multiple genes with roles in sex steroid metabolism, olfaction and drug response. These common deletion polymorphisms typically represent ancestral mutations that are in linkage disequilibrium with nearby SNPs, meaning that their association to disease can often be evaluated in the course of SNP-based whole-genome association studies.

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Acknowledgements

The authors wish to thank J. Moore and L. Ziaugra for contributing their expertise on the behavior of genotyping platforms and C. Patil, J. Melo and E. Lander for commenting on manuscript drafts. We thank G. Thorisson and A. Vernon-Smith for extensive help with data coordination, and D. Conrad, J. Pritchard and K. Frazer for exchanging manuscripts before publication.

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Authors and Affiliations

  1. Department of Molecular Biology, Massachusetts General Hospital, 55 Fruit Street, Boston, 02114, Massachusetts, USA
    Steven A McCarroll, Tracy N Hadnott & David M Altshuler
  2. Center for Human Genetic Research, Massachusetts General Hospital, 55 Fruit Street, Boston, 02114, Massachusetts, USA
    Steven A McCarroll, Mark J Daly & David M Altshuler
  3. Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, 02141, Massachusetts, USA
    Steven A McCarroll, Pardis C Sabeti, Michael C Zody, Jeffrey C Barrett, Stacey B Gabriel, Mark J Daly & David M Altshuler
  4. Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, 02115, Massachusetts, USA
    George H Perry, Stephanie Dallaire & Charles Lee
  5. Harvard Medical School, Boston, 02115, Massachusetts, USA
    Charles Lee, Mark J Daly & David M Altshuler
  6. Department of Medicine, Massachusetts General Hospital, Simches Research Center, 185 Cambridge St., Boston, 02114, Massachusetts, USA
    Mark J Daly & David M Altshuler

Authors

  1. Steven A McCarroll
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  2. Tracy N Hadnott
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  3. George H Perry
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  4. Pardis C Sabeti
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  5. Michael C Zody
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  6. Jeffrey C Barrett
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  7. Stephanie Dallaire
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  8. Stacey B Gabriel
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  9. Charles Lee
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  10. Mark J Daly
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  11. David M Altshuler
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  12. The International HapMap Consortium
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Correspondence toDavid M Altshuler.

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McCarroll, S., Hadnott, T., Perry, G. et al. Common deletion polymorphisms in the human genome.Nat Genet 38, 86–92 (2006). https://doi.org/10.1038/ng1696

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